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Cytidine 5′-Diphosphocholine (CDP-Choline) in Stroke and Other CNS Disorders

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Abstract

Brain phosphatidylcholine (PC) levels are regulated by a balance between synthesis and hydrolysis. Pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1α/β) activate phospholipase A2 (PLA2) and PC-phospholipase C (PC-PLC) to hydrolyze PC. PC hydrolysis by PLA2 releases free fatty acids including arachidonic acid, and lyso-PC, an inhibitor of CTP-phosphocholine cytidylyltransferase (CCT). Arachidonic acid metabolism by cyclooxygenases/lipoxygenases is a significant source of reactive oxygen species. CDP-choline might increase the PC levels by attenuating PLA2 stimulation and loss of CCT activity. TNF-α also stimulates proteolysis of CCT. TNF-α and IL-1β are induced in brain ischemia and may disrupt PC homeostasis by increasing its hydrolysis (increase PLA2 and PC-PLC activities) and inhibiting its synthesis (decrease CCT activity). The beneficial effects of CDP-choline may result by counteracting TNF-α and/or IL-1 mediated events, integrating cytokine biology and lipid metabolism. Re-evaluation of CDP-choline phase III stroke clinical trial data is encouraging and future trails are warranted. CDP-choline is non-xenobiotic, safe, well tolerated, and can be considered as one of the agents in multi-drug treatment of stroke.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Wisconsin, Madison, WI

    Rao Muralikrishna Adibhatla & J. F. Hatcher

  2. Cardiovascular Research Center, University of Wisconsin, Madison, WI

    Rao Muralikrishna Adibhatla

  3. Veterans Administration Hospital, Madison, WI

    Rao Muralikrishna Adibhatla

  4. Department of Neurological Surgery, Clinical Science Center, University of Wisconsin-Madison, H4-330, 600 Highland Avenue, Madison, WI, 53792-3232

    Rao Muralikrishna Adibhatla

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  1. Rao Muralikrishna Adibhatla
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  2. J. F. Hatcher
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Correspondence to Rao Muralikrishna Adibhatla.

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Adibhatla, R.M., Hatcher, J.F. Cytidine 5′-Diphosphocholine (CDP-Choline) in Stroke and Other CNS Disorders. Neurochem Res 30, 15–23 (2005). https://doi.org/10.1007/s11064-004-9681-8

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  • DOI: https://doi.org/10.1007/s11064-004-9681-8

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